Gastrointestinal neuromuscular diseases (GINMDs) comprise a heterogenous group of chronic conditions associated with impaired gut motility. These gastrointestinal (GI) disorders, differing for etiopathogenic mechanisms, pathologic lesions, and region of gut involvement, represent a relevant matter for public health, because they are very common, can be disabling, and determine major social and economic burdens. GINMDs are presumed or proven to arise as a result of a dysfunctioning GI neuromuscular apparatus, which includes myenteric ganglia (neurons and glial cells), interstitial cells of Cajal and smooth muscle cells. Despite the presence of symptoms related to gut dysmotility in the clinical phenotype of these patients, in the diagnostic setting scarce attention is usually paid to the morphologic pattern of the GI neuromuscular apparatus. It is also objectively difficult to collect full-thickness gut tissue samples from patients with GINMDs, because their disease, which can be only functional in nature, may not justify invasive diagnostic procedures as a first-line approach. As a consequence, whenever available, bioptic gut specimens, retrieved from these patients, must be regarded as a unique chance for obtaining relevant diagnostic information. On the basis of these arguments, there is an urgent need of standardized and validated histopathologic methods, aiming at overcoming the discrepancies affecting current approaches, which usually lead to conflicting definitions of normality and hamper the identification of disease-specific pathologic patterns. This review article intends to address current methodological and ontological issues in the histopathologic diagnosis of GINMDs, to foster the debate on how to discriminate normal morphology from abnormalities.
*Unit of Histology
§Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa
†Section of Gastroenterology and Hepatology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia
‡Second Section of Pathology, Spedali Civili, Brescia, Italy
Supported by an institutional research grant issued by the Interdepartmental Center for Research in Clinical Pharmacology and Experimental Therapeutics, University of Pisa, Pisa, Italy.
All figures can be viewed online in color at http://www.anatomicpathology.com.
The authors have no conflicts of interest to disclose.
Reprints: Nunzia Bernardini, MD, Unit of Histology, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 55, I-56126 Pisa, Italy (e-mail: firstname.lastname@example.org).